The Biomedical Image Analysis and Services Section (BIRSS) is committed to providing computational and engineering expertise to a variety of clinical and biomedical informatics activities at NIH. Specifically, biomedical imaging research in PET, ultrasound, CT, MRI, microscopy, cancer research, and neural dysfunction have been supported extensively. To advance and empower scientific research in the NIH intramural program, CIT has developed and continues to enhance a sophisticated open source, platform-independent, n-dimensional, extensible image processing and visualization application. The MIPAV (Medical Image Processing Analysis and Visualization) (http://mipav.cit.nih.gov/) is an application that enables quantitative analysis and visualization of biomedical imaging modalities (from micro to macro) and is used by researchers at NIH and around the world. At NIH, MIPAV has been used to analyze anatomical structures in CT datasets, analysis of MRI datasets for NIMH, and has been used by NCI for the analysis of 2D and 3D microscopic samples. In addition, BIRSS leads the development of the Biomedical Research Informatics Computing System (BRICS) (http://brics.cit.nih.gov/) which is a collaborative and extensible web-based system to support the collection and analysis of research studies and clinical trials, using a set of modular components that cover all stages of the research life cycle. And because BRICS is un-branded and not associated with a particular disease or organization, it can be efficiently custom-tailored for many research programs. MIPAV's integrated set of biomedical imaging algorithms and its extensibility have been used by BIRSS to implement many solutions to imaging problems in the NIH intramural research community. To create custom workflows and solutions for intramural collaborators, BIRSS team members can build plug-ins that leverage the algorithms and tools in MIPAV to solve complex imaging research questions. For example, BIRSS continues to develop a novel MIPAV plug-in as part of a collaboration with Dr. Hari Shroffs lab in the National Institute of Biomedical Imaging and Bioengineering (NIBIB) to untwist four-dimensional high-resolution microscopy images of the Caenorhabditis elegans nematode embryo throughout its development. This plug-in used the image registration and visualization tools already developed by BIRSS for MIPAV, along with novel fiducial annotation and lattice warping tools, to allow the NIBIB researchers to annotate and regularize the C. elegans embryo data through its twitching phase of development, which has not previously been possible algorithmically. This, in turn, allowed Dr. Shroffs group to investigate neurodevelopmental events in late embryogenesis and apply it to track the 3D positions of seam cell nuclei, neurons, and neurites in multiple elongating embryos. The detailed positional information obtained enabled NIBIB to develop a composite model showing movement of these cells and neurites in an 'average' worm embryo. The untwisting and cell tracking capabilities of this plug-in provides a foundation on which to catalog C. elegans neurodevelopment, allowing interrogation of developmental events in previously inaccessible periods of embryogenesis. Accurate automatic organ segmentation is an important yet challenging task for medical image analysis. Anatomical variability in shape and texture feature inhibits traditional segmentation methods from achieving high accuracies. Machine learning has dominated the medical imaging research field in the past decade. Initially, pioneer work with decent feature extraction and SVM based image classification achieves better results. Later, learning based detection algorithm began to dominate the machine learning tools like boosting trees, random forest. More recently the deep learning based Deep Convolutional Neural Networks (DCNNs) become the mainstream of the medical imaging research field for the past two years. Using and enhancing the MIPAV application has allowed us to rapidly build the new machine learning component integral to the MIPAV software and is being used to support automated segmentation of the prostate. BIRSS also leads the development of the Biomedical Research Informatics Computing System (BRICS) (http://brics.cit.nih.gov/) which is a collaborative and extensible web-based informatics system to support the collection and analysis of research studies and clinical trials. BRICS is un-branded and not associated with a particular disease or organization, therefore, it can be efficiently custom-tailored for many research programs. For example, in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS), BIRSS has developed two informatics systems, using the BRICS system, in support of Traumatic Brain Injury (TBI)(http://fitbir.nih.gov/)research, the Parkinsons Disease Biomarker Program (PDBP) (http://pdbp.ninds.nih.gov/), as well as, collaborated with the National Eye Institute developed an informatics system for rare eye diseases, eyeGENE (https://eyegene.nih.gov/). The TBI informatics system is called the Federal Interagency TBI Research (FITBIR) database to acknowledge the interagency participation and shared interests. FITBIR serves as a repository for TBI research, is supported by multiple federal agencies, and consolidates high quality, uniformly collected, and contemporary data that can be accessed and analyzed by scientific experts. Over one million records have been uploaded to FITBIR thus far for 66,00 subjects enrolled in 105 different research studies. Currently there are 145 studies expected to contribute to FITBIR and the number of studies is growing every year. Within FITBIR are clinical outcome data and imaging data of which 36,000+ records are of imaging data (MRI, CT, PET and Diffusion) from 45,000+ individual subjects. A summary of the data can be found here: https://fitbir.nih.gov/content/submitted-data. The goal of the PDBP, a BRICS system, is to support new and existing research and resource development promoting biomarker discovery for Parkinson's disease. Although our understanding of the biology and genetics associated with Parkinson's disease (PD) is advancing rapidly, gaps remain between promising laboratory discoveries and the realization of treatments that will cure or slow progression of PD. To address the needs of the PD community, NINDS has established the PDBP program focused on promoting the discovery of biomarker candidates for early detection and measurement of disease progression. To date, the PDBP prospective consortium has 100% accrual at nine sites across the US with more than 1,600 enrolled subjects of which biorepository samples have been collected from 1,501 subjects. A summary of the data can be found here: https://pdbp.ninds.nih.gov/Data The National Eye Institute (NEI) has also adopted the BRICS system to support The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE) (https://eyegene.nih.gov/). The eyeGENE project is a research venture created by NEI in response to promising scientific discoveries in genetics. eyeGENE aims to advance studies of eye diseases and their genetic causes by giving researchers access to DNA samples, clinical information, and patients looking to participate in research studies and clinical trials. A summary of the data can be found here: https://eyegene.nih.gov/node/35.